International Journal of Medical Sciences

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26 April 2018

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Int J Med Sci 2018; 15(7):666-673. doi:10.7150/ijms.23940

Research Paper

ICOS signal facilitates Foxp3 transcription to favor suppressive function of regulatory T cells

Qianmei Chen#, Lijun Mo#, Xiangsheng Cai, Lili Wei, Zhengneng Xie, Hongwei Li, Jinlong Li, Zhiming Hu

Institute of Biotherapy, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China
# These authors contributed equally to this work.

Abstract

Inducible costimulator (ICOS) plays an important role in the suppressive immunity mediated by regulatory T cells (Tregs), but the molecular regulation mechanism is not well known. Here we performed a study to explore the possible mechanism by which ICOS regulates the suppressive functions and survival of Tregs. This study showed that both the ICOS and CD28 signal could promote the survival of Tregs. However, ICOS but not CD28 improved the suppressive function of Tregs. Mechanistic studies demonstrated that ICOS could induce the transcription activity of Foxp3, by facilitating the nuclear factor of activated T cells (NFAT): Foxp3 over NFAT: activator protein 1 (AP-1). The results of Q-PCR showed that AP1 downstream regulatory genes (IL-2 and IL-6) were down-regulated, and Foxp3 downstream regulatory genes (IL-4, IL-10 and TGF-β) were up-regulated. Further, ICOS promoted anti-apoptosis may be by activating protein kinase B (Akt) signal. These findings demonstrated that ICOS signal could facilitate Foxp3 transcription in favor of survival and suppressive function of Tregs.

Keywords: Tregs, ICOS, Immunosuppression

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How to cite this article:
Chen Q, Mo L, Cai X, Wei L, Xie Z, Li H, Li J, Hu Z. ICOS signal facilitates Foxp3 transcription to favor suppressive function of regulatory T cells. Int J Med Sci 2018; 15(7):666-673. doi:10.7150/ijms.23940. Available from http://www.medsci.org/v15p0666.htm